Abstract LB-191: Cytological atypia predicts short-term breast cancer risk in women from high-risk families that lack a BRCA mutation.

Abstract

Abstract Background: Women with deleterious mutations in BRCA1/2 have a 9- to 36-fold increased risk of breast cancer compared with general population rates. However, there are a significant number of women whose families have multi-generation premenopausal breast cancers and lack an identified BRCA-mutation. Currently we lack strategies to predict the development of breast cancer in women from BRCA-negative families. Random Periareolar Fine Needle Aspiration (RPFNA) is a research technique developed to test for “field effects” in high-risk women. Carol Fabian previously demonstrated that atypia in RPFNA predicted breast cancer risk, however, many women in this cohort were known BRCA mutation carriers. We investigated whether cytological atypia in RPFNA predicts the subsequent development of breast cancer in women from BRCA-negative breast cancer families. Results: From 01/01/03 to 07/01/12, we performed RPFNA in 254 high-risk BRCA-negative women. Women underwent yearly mammogram/Magnetic Resonance Imaging (MRI) and bi-annual clinical breast exam. During 6.5 women-years of follow-up, 24 new breast cancers were diagnosed. The median age of the 254 women in this study was 48, and the median BMI was 24. Eighty-six percent (218) of the women were Caucasian, 13% (32) were African-American, and 2 women were Native Americans. Sixty-eight women presented with cytologic-atypia in at least one breast; 16 of these women had cytologic-atypia in both breasts. Fourteen (21%) of the 68 women with baseline cytologic-atypia later developed cancer in a breast that had had baseline cytologic-atypia; none of the 68 women developed cancer in a breast without baseline cytologic-atypia. One hundred eighty-six women did not have cytologic-atypia at baseline; 10 (5%) of these women developed cancer. Ten women had a prophylactic mastectomy and were censored at the date of mastectomy. The median length of follow-up among the uncensored patients was 74 months. In the baseline atypic and non-atypic groups, the 48-month cumulative incidence of cancer development was 0.22 (95% confidence interval [CI], 0.13-0.34) and 0.04 (95% CI, 0.02-0.08), respectively. Atypia was significantly associated with cancer development both with and without controlling for covariates (p < 0.001). The covariate-adjusted hazard ratio (CV-AHR) for cytologic-atypia was 6.3 (95% CI, 1.7-24.2). The hazard ratios for the covariates were as follows: age (1.01; 95% CI, 0.89-1.16), BMI (1.02; 95% CI, 0.91-1.15), menopausal status (0.16; 95% CI, 0.01-2.60), Gail Risk (1.18; 95% CI, 1.03-1.35) and mammographic density for scattered (1.7; 95% CI, 0.27-10.9) and heterogenetic (1.10; 95% CI, 0.20-6.01) compared to the reference type of extreme. Conclusions: This is the first demonstration that in women from high-risk BRCA mutation-negative families, cytologic-atypia in RPFNA is associated with the subsequent development of breast cancer. Citation Format: Victoria L. Seewaldt, Bercedis Peterson, Gloria Broadwater. Cytological atypia predicts short-term breast cancer risk in women from high-risk families that lack a BRCA mutation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-191. doi:10.1158/1538-7445.AM2013-LB-191